Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I

Small nuclear RNAs (snRNAs) are essential factors in messenger RNA splicing. By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities. Functional assays showed that mutations (30G>A, 51G>A, 55G>A, and 111G>A) associated with MOPD I cause defective U12-dependent splicing. Endogenous U12-dependent but not U2-dependent introns were found to be poorly spliced in MOPD I patient fibroblast cells. The introduction of wild-type U4atac snRNA into MOPD I cells enhanced U12-dependent splicing. These results illustrate the critical role of minor intron splicing in human development.     

INTRAVERTEBRAL DISC HERNIATION (SCHMORL'S NODE) IN FIVE DOGS

The herniation of intervertebral disc material into the vertebral body, known as Schmorl's nodes, is a well described disease process in man. Schmorl's nodes have not until now been described in the dog. This paper describes intravertebral disc herniation in the dog based on five patients taken from a retrospective study of dogs suspected of having cauda equina syndrome. The significance of intravertebral disc herniation in the dog at this time is that they indicate a disturbance in the vertebral endplate, they present definite radiographic signs, should be considered in patients with ostecohondrosis, and remain a possibls etiology for fibrocartilaginous emboli. Back pain is a common sign in people when Schmorl's nodes were the only pathologic findings. The common signs of palpatory pain in the lumbosacral region of the dogs in this report is noted but cannot be directly correlated at this time to the intravertebral disc herniation; however, it is suspected in two of the cases.     

Aryldiones incorporating a [1,4,5]oxadiazepane ring. Part 2: chemistry and biology of the cereal herbicide pinoxaden

BACKGROUND: Pinoxaden is a new cereal herbicide that provides outstanding levels of post‐emergence activity against a broad spectrum of grass weed species for worldwide selective use in both wheat and barley. RESULTS: Factors influencing activity and tolerance to pinoxaden were in part linked to distinct structural parts of the active ingredient. Three complementary contributions that decisively impact upon the herbicidal potency against grasses were identified: a preferred 2,6‐diethyl‐4‐methyl aromatic substitution pattern, a dione area suitable for proherbicide formation and beneficial adjuvant effects. The uptake and translocation pattern of pinoxaden when coapplied with its tailored adjuvant were analysed by autoradiography, indicating extensive and rapid penetration, followed by effective distribution throughout the plant. Crop injury reduction on incorporation of the [1,4,5]oxadiazepane ring into the aryldione template was reinforced with safener technology. Comparative studies on the behaviour of pinoxaden applied either alone or in combination with the safener cloquintocet‐mexyl demonstrated that addition of the safener resulted in significant enhancement of metabolic degradation in wheat and barley, providing excellent crop tolerance and a substantial selectivity margin without adverse effects on weed control. CONCLUSION: The biological potential of pinoxaden and its active principle pinoxaden dione in terms of grass weed control and tolerance in cereals was fully exploited by inclusion of the safener cloquintocet‐mexyl in the formulation in combination with a specific and tailor‐made tank‐mix adjuvant based on methylated rape seed oil. Copyright © 2011 Society of Chemical Industry